EAL

GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to investigate the insulin response to a 3-hour glucose tolerance test and to compare the insulin level in the gestational diabetes mellitus and single abnormal test value groups with a nondiabetic control group.

Inclusion Criteria:

110 Turkish women with uncomplicated pregnancy participated in this prospective control study between 24 and 28 weeks of gestation.
The study was approved by the institutional review board of the university, and informed consent was obtained from each patient just before entering the study

Exclusion Criteria:

The exclusion criteria was not delineated.

Description of Study Protocol:

Recruitment : In the clinic, all pregnant women are routinely screened for GDM between 24 and 28 weeks of gestation.

Design :Case control

After an abnormal 50g glucose screening test was obtained, patients were placed into 1 of 3 groups according to the results obtained from the OGTT:

Group 1 comprised patients with normal 3-hour 100g OGTT values
Group 2 comprised patients with one abnormal test value (single value abnormality)
Group 3 comprised patients with GDM with 2 or more abnormal test values

Blinding used (if applicable): not applicable

Intervention : To assure consistency in testing procedures, all women instructed to add 150 g of carbohydrate to their usual meals for each 3 days before the the OGTT.

Statistical Analysis

To determine the sample size, a power analysis with 99% confidence level (1-alpha) and 95% power (1-Beta) was done , considering the fact that 455 of the patients with a single value abnormality during OGTT has GDM. According to the power analysis, a sample of 50 individuals from the normal OGTT group, 20 individuals from the single value abnormality group, and 16 individuals from the GDM group would be enough to show the differences between these groups.

Data were expressed as mean + SD.
Statistical analysis was performed by the Student t test and 1-way analysis test with posthoc Bonferroni correction.
Differences were considered statistically significant at a level of probability of <.05.

Data Collection Summary:

Timing of Measurements

Samples were collected at 8 am (12-h fasting state) and at 60, 120, and 180 minutes after glucose ingestion.

Dependent Variables

Plasma glucose levels were measured by the use of the glucose oxidase method
Plasma insulin concentrations were measured by Microparticle Enzyme Immunoassay method (AxSYM insulin assay: Abbott, Tokoyo, Japan).
The OGTT results were interpreted according to the criteria of Carpenter and Coustan. The tests were considered positive if the fasting and the 1-, 2-, and 3-hour plasma glucose levels were >95 , 180, 155 and 140, respectively .
GDM was diagnosed when 2 or more of the plasma glucose values exceeded these limits.

Independent Variables

Age
Parity
Obesity
Body Mass Index (BMI) was calculated as the ratio between weight (kg) and height (m)² ; patients were considered obese if their BMI was > 27.
Insulinogenic index was used as an index of early phase insulin secretion in the OGTT. The index was defined as the ratio of the increment of insulin to that of plasma glucose 60 minutes after glucose load ( delta 0-60/delta PG 0-60).
Total insulin secretion- defined as the mean insulin resistance index during the OGTT (0-180 minutes).
Insulin resistance-was analyzed according to the homeostasis model assessment (HOMA).
Homeostasis Model Assessment (HOMA)- the formula used to calculate the HOMA model was as follows: fasting insulin (µU/mL) x fasting glucose (mmol/L)/22.5.

Control Variables

Description of Actual Data Sample:

Initial N: 110 pregnant women

Attrition (final N): 110

Age: See Table I

Ethnicity:

Other relevant demographics:

Anthropometrics

Location: Department of Obstetrics and Gynecology, Bashent University, Turkey

Summary of Results:

Patients in groups 2 and 3 were older than those in group 1 (P<.001) for both) (Table I).

Table I. Patient characteristics

Characteristics	Group 1 (normal OGTT)	Group 2 (single abnormal value)	Group 3 (GDM)
Age (y,mean± SD)	26.5±3.0	30.7±4.1*	30.6±3.8♦
Parity (%)	-	-	-
0	32	34	33
1-2	53	52	48
>3	15	14	19
Obesity (BMI;wt(kg)/ ht(m)²; mean±SD)	23.1±4.5	24.9±3.5	25.4±3.7€
BMI>27(%)	16	35	32.5

*P<.001, group 2 versus group 1

♦P<.001, group 3 versus group 1.

£ P<.05, group 3 versus group 1.

When the proportion of abnormal single glucose values during OGTT was assessed, it was found that the abnormal value was 30% at fasting, 40% at 1 hour, 15% at 2 hours, and 15% at 3 hours. The worsening glycemic profile from normal OGTT to GDM was associated with an increase of fasting insulin levels (Table II).

Table II. Plasma glucose levels during OGTT in the 3 study groups across time

Variable	Group 1 (normal OGTT)	Group 2 (single abnormal value)	Group 3 (GDM)
Fasting (mmol/L; mean±SD)	81.8±7.0	92.4±13.08*	102.3±16.1♦£
60-Min (mmol/L; mean± SD)	128.1 ±24.5	169.4±23.0§	212.2±49.3♦\|
120 Min (mmol/L;mean±SD)	114.0±18.5	133.3±15.3§	175.9±48.0♦\|
180-Min (mmol/L;mean±SD)	99.1±19.1	107.7±26.5	125.1±39.2♦

Note: Data are given as mean±SD.

* P< .005, group 2 versus group 1

♦ P< .001 ,group 3 versus group 1

£ P<.05, group 3 versus group 2

§ P<.001, group 2 versus group 1.

| P< .001, group 3 versus group 2.

There was a significant difference in fasting insulin levels when GDM and single value abnormality groups were compared with the normal OGTT group (P<.001 and P< .005, respectively). The worsening glycemic profile from normal OGTT to GDM was associated with a significant increase in total secretion (Table III).

Table III. The plasma insulin levels and total insulin secretion (mean insulin value) during OGTT in the 3 study groups across time

Variable	Group 1 (normal OGTT)	Group 2 (single abnormal value)	Group 3 (GDM
Fasting (mmol/L)	6.5±2.7	8.8±3.1*	9.4±2.8 ♦
1-Hour (mmol/L)	65.7±30.3	105.9±83.2*	124.5±68.7♦
2-Hour (mmol/L)	61.3±38.7	95.4±32.8 €	150.5±87.7♦§
3-Hour (mmol/L)	47.2±39.3	49.4±23.6	77.5±45.3♦\|
Total insulin secretion (mmol/L) ¶	45.1±22.4	64.8±27.8#	88.4±45.5♦**

Note: Data are given as mean±SD.

* P< .05, group 2 versus group 1

♦ P< .001 ,group 3 versus group 1

€ P<.001, group 2 versus group 1

§ P<.001, group 3 versus group 2.

| P< .005, group 3 versus group 2.

¶ Mean insulin value

#P< .005,group 2 versus group 1.

**P <.05 , group 3 versus group 2.

Other Findings

Mean homeostasis model assessment (HOMA) insulin resistance (IR) was higher in the GDM group than in the normal OGTT group (P<.001).
The mean HOMA IR of the single value abnormality group was also higher than the normal OGTT group (P<.005).
There was a significant difference in insulinogenic index only when the normal OGTT group was compared with the GDM group (P<.05).

Author Conclusion:

The findings suggest that a singleton abnormal test value on an oral glucose tolerance test should be regarded as a pathological finding and that the patient with a single abnormal test value must be treated similarly to the patient with gestational diabetes mellitus.

Limitations: patients with single value abnormalities were indistinguishable from patients with GDM and significantly different from the values for the normal OGTT group, by means of the fasting insulin levels and the insulin resistance. Therefore, the data that we have presented strongly supported the need to continue to refine the existing diagnostic criteria for GDM.

Funding Source:

Reviewer Comments:

Inclusion/exclusion criteria and recruitment methods not well described.

The limitations and critique of the study, as stated by the authors appear to be very appropriate.

Case control studies are studies in which patients who already have a certain condition are compared with people who do not. Case control studies are less reliable than cohort studies. Just because there is a statistical relationship between two conditions does not mean that one condition actually caused the other.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	???
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	N/A
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes